Aquaresis Utility for Hyponatremic Acute Heart Failure Study

NCT02183792 | Completed Phase 4 Results

• 1 other identifier: HS-13-00705
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

Hyponatremia is a common finding in acute heart failure (HF) patients and is associated with worse prognosis. In addition to its prognostic value, hyponatremia may have importance during the acute management of HF. We've recently shown that acute or chronic hyponatremia, especially \<130 mEq/L, was associated with higher loop diuretic dose requirements and more frequent need for escalation of the diuretic regimen to achieve the same level of diuresis as normonatremic HF patients. Aquaresis with tolvaptan represents a potentially advantageous approach to the management of volume overload in HF, especially in patients presenting with concomitant hyponatremia. The purpose of the current study is to prospectively evaluate the comparative efficacy and safety of a tolvaptan-based diuretic regimen compared to conventional diuresis with a furosemide-based regimen on short-term clinical and treatment outcomes in hyponatremic acute HF patients. This will be a prospective, open-label, parallel-group, randomized study comparing a tolvaptan-based aquaretic regimen to a conventional continuous infusion loop diuretic-based regimen of furosemide. Up to 55 (target sample size of 50) adult subjects admitted with acute HF and signs of volume overload, and serum sodium less than 135 mEq/L will be randomized to tolvaptan or furosemide treatment arms. The initial 24 hours of study treatment will compare tolvaptan monotherapy to furosemide monotherapy. After the initial 24 hours, treatment regimens may be altered to achieve desired clinical goals. Patients will be followed for up to 96 hours and at discharge for study purposes.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Median Urine Output at 24 Hours Post Randomization

  24 hours post randomization

Secondary Outcomes (1)

• Median Change in Serum Creatinine at 24 Hours Post Randomization

  24 hours post randomization

Other Outcomes (18)

• Total Urine Output

  Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days

• Glomerular Filtration Rate (Estimated)

  Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days

• In-hospital Mortality

  Participants will be followed for the duration of hospital stay, an expected average of 5 days

Study Arms (2)

Tolvaptan

EXPERIMENTAL

Tolvaptan 30-60mg once daily (with rescue loop diuretic or metolazone)

Drug: Tolvaptan

Furosemide

ACTIVE COMPARATOR

Furosemide continuous infusion 5mg/h with option to titrate (with rescue metolazone)

Drug: Furosemide

Interventions

Tolvaptan DRUG

Also known as: Samsca

Tolvaptan

Furosemide DRUG

Also known as: Lasix

Furosemide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute HF with signs or symptoms of volume overload \[i.e. elevated jugular venous pulsation (JVP), rales, edema\]
• Serum sodium \< 135 mEq/L at time of or within first 48 hours of hospitalization
• Randomized within 48 hours of presentation to hospital
• ≥ 18 years of age
• Informed consent

You may not qualify if:

• Severe symptomatic hyponatremia requiring acute treatment
• Severe renal impairment upon admission (creatinine clearance \< 20 mL/min)
• Renal replacement therapy dependent, or requiring upon admission
• Acute coronary syndrome on admission
• Requires or has a mechanical circulatory support device
• Evidence of cardiogenic shock requiring intravenous vasopressors
• Pregnancy
• Patient requiring concomitant use of strong CYP3A4 inhibitors (clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin)

Sponsors & Collaborators

• University of Southern California: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (2)

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Tolvaptan; Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Tien Ng, Pharm.D.
• Organization: University of Southern California School of Pharmacy

tienng@usc.edu

3234421840

Study Officials

• Tien Ng, PharmD

  University of Southern California

  PRINCIPAL INVESTIGATOR

• Uri Elkayam, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Pharmacy and Medicine

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 8, 2014
• Study Start: December 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: March 1, 2018
• Last Updated: May 28, 2019
• Results First Posted: May 28, 2019

Record last verified: 2019-05

Locations

US (2)